This program is aimed at the synthesis and antitumor evaluation of a series of 6-vinyluracil derivatives and is intended to amplify and extend the recent finding that 5'-methylene-6,5'-cyclouridine and 6-vinyluracil are active in vivo against a number of experimental tumors in mice. Specifically, seven classes of compounds are proposed: A) 6-vinyluracils substituted at C-5 and/or the vinyl group with electron donating and electron withdrawing groups, B) substituted 6-ethyluracils that have the potential to undergo elimination in vivo to give the 6-vinyl derivatives, C) 5-substituted-6-vinyl-cytosines, D) 6-vinyluridine and related nucleosides, including the 2'-deoxy analogs, E) 5', 6'-unsaturated-6,5'-cyclopyrimidine nucleosides, F) 5-substituted uracil-6-acrylic esters and G) 5-substituted uracil-6-propiolate esters. Since the lead compounds react readily with thiols and may function in vivo as alkylating agents, the overall goal is to determine whether the antitumor activity can be increased by altering their suceptibility attack. The new compounds are expected to vary considerably in the rates (and sometimes the sites) at which they react with thiols and attempts will be made to correlate this information with observed in vitro and in vivo antitumor activity. All of the new compounds will be examined for in vitro activity against mouse leukemia cells in culture and for antibacterial activity against Streptococcus faecalis. Active compounds will be evaluated for in vivo activity in mice bearing a variety of leukemias and solid tumors, using both sensitive and resistant tumor lines. The new 2'-deoxy nucleosides will be examined for in vitro activity against Herpes simplex virus growing in tissue culture cells.